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Showing drug card for Fluvastatin (DB01095)

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Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:03:39
Primary Accession Number DB01095
Secondary Accession Number
  • APRD00346
Name Fluvastatin
Drug Type
  • Approved
  • Small Molecule
Description Fluvastatin is a member of the drug class of statins, used to treat hypercholesterolemia and to prevent cardiovascular disease.
Synonyms
  1. Fluindostatin
  2. Fluvastatina [INN-Spanish]
  3. Fluvastatine [INN-French]
  4. Fluvastatinum [INN-Latin]
Brand Names
  1. Canef
  2. Cranoc
  3. Lescol
  4. Lescol XL
Brand Mixtures Not Available
Chemical IUPAC Name (E,3S,5R)-7-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3,5-dihydroxyhept-6-enoic acid
Chemical Formula C24H26FNO4
Chemical Structure Structure
CAS Registry Number 93957-54-1
InChI Identifier InChI=1/C24H26FNO4/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30)/b12-11+/t18-,19-/m0/s1/f/h29H
InChI Key FJLGEFLZQAZZCD-IZGCACMCDM
KEGG Drug Not Available
KEGG Compound C07014 Link Image
PubChem Compound 1548972 Link Image
PubChem Substance 206649 Link Image
ChEBI ID 5136 Link Image
PharmGKB ID PA449688 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02250527 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/fluvastatinxl.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Fluvastatin Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference F. G. Kathawala, U.S. Pat. 4,739,073 (1988)
Average Molecular Weight 411.4659
Monoisotopic Molecular Weight 411.1846
State Solid
Melting Point 194-197oC
Experimental Water Solubility 0.46 mg/L Source: PhysProp
Predicted Water Solubility 4.41e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 4.5 Source: PhysProp
Predicted LogP 3.69 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.97 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC(C)N1C2=CC=CC=C2C(C2=CC=C(F)C=C2)=C1\C=C\[C@H](O)C[C@H](O)CC(O)=O
Canonical SMILES CC(C)N1C2=CC=CC=C2C(C2=CC=C(F)C=C2)=C1C=CC(O)CC(O)CC(O)=O
Drug Category
  • Anticholesteremic Agents
  • Antioxidants
  • Free Radical Scavengers
  • HMG-CoA Reductase Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
ATC Codes
AHFS Codes
  • 24:06.08
Indication For management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia
Pharmacology Fluvastatin, the first synthetically-prepared HMG-CoA reductase inhibitor, is used as an antilipemic to lower cholesterol and triglyceride levels associated with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb) and to slow the progression of coronary atherosclerosis in patients with coronary artery disease. Although similar to lovastatin, simvastatin, and pravastatin, Fluvastatin has a shorter half-life, no active metabolites, extensive protein binding, and minimal CSF penetration.
Mechanism of Action Fluvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, this results in a decrease in mevalonate, a precursor of cholesterol, and a subsequent decrease in hepatic cholesterol levels and increase in uptake of LDL cholesterol.
Absorption 24% (range 9%-50%).
Toxicity Variety of GI complaints and an increase in transaminase values (i.e., SGOT and SGPT).
Protein Binding 98%
Biotransformation Hepatic
Half Life 2.5 hours
Dosage Forms
Form Route
Capsule Oral
Tablet, extended release Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol The statin increases the anticoagulant effect
Anisindione The statin increases the anticoagulant effect
Bezafibrate Increased risk of myopathy/rhabdomyolysis
Cholestyramine Increased/decreased effect according to spacing
Colchicine Increased risk of rhabdomyolysis with this combination
Colestipol Increased/decreased effect according to spacing
Cyclosporine Possible myopathy and rhabdomyolysis
Dicumarol The statin increases the anticoagulant effect
Fenofibrate Increased risk of myopathy/rhabdomyolysis
Fluconazole Fluconazole increases the effect and toxicity of fluvastatin
Gemfibrozil Increased risk of myopathy/rhabdomyolysis
Rifabutin The rifamycin decreases the effect of statin drug
Rifampin The rifamycin decreases the effect of statin drug
Warfarin The statin increases the anticoagulant effect
Food Interactions
  • May be taken with or without food, but should be taken consistently.
Pathways
Name SMPDB Link KEGG Link
Fluvastatin Pathway SMP00119 Link Image
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2C8 (CYP2C8)
  2. Cytochrome P450 2C9 (CYP2C9)
  3. Cytochrome P450 1A1 (CYP1A1)
Targets
  1. 3-hydroxy-3-methylglutaryl-coenzyme A reductase
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2C8 (CYP2C8)
Enzyme 1 Gene Name CYP2C8
Enzyme 1 SwissProt ID P10632 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P10632|CP2C8_HUMAN Cytochrome P450 2C8 (EC 1.14.14.1) 
MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKV
YGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRW
KEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICS
VVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALT
RSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTE
TTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSD
LVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFK
KSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLP
PSYQICFIPV
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 2C9 (CYP2C9)
Enzyme 2 Gene Name CYP2C9
Enzyme 2 SwissProt ID P11712 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P11712|CP2C9_HUMAN Cytochrome P450 2C9 (EC 1.14.13.80) 
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
PFYQLCFIPV
Phase 1 Metabolizing Enzyme 3 [top]
Enzyme 3 Name Cytochrome P450 1A1 (CYP1A1)
Enzyme 3 Gene Name CYP1A1
Enzyme 3 SwissProt ID P04798 Link Image
Enzyme 3 SNPs SNPJam Report Link Image
Enzyme 3 Protein Sequence >sp|P04798|CP1A1_HUMAN Cytochrome P450 1A1 (EC 1.14.14.1) 
MLFPISMSATEFLLASVIFCLVFWVIRASRPQVPKGLKNPPGPWGWPLIGHMLTLGKNPH
LALSRMSQQYGDVLQIRIGSTPVVVLSGLDTIRQALVRQGDDFKGRPDLYTFTLISNGQS
MSFSPDSGPVWAARRRLAQNGLKSFSIASDPASSTSCYLEEHVSKEAEVLISTLQELMAG
PGHFNPYRYVVVSVTNVICAICFGRRYDHNHQELLSLVNLNNNFGEVVGSGNPADFIPIL
RYLPNPSLNAFKDLNEKFYSFMQKMVKEHYKTFEKGHIRDITDSLIEHCQEKQLDENANV
QLSDEKIINIVLDLFGAGFDTVTTAISWSLMYLVMNPRVQRKIQEELDTVIGRSRRPRLS
DRSHLPYMEAFILETFRHSSFVPFTIPHSTTRDTSLKGFYIPKGRCVFVNQWQINHDQKL
WVNPSEFLPERFLTPDGAIDKVLSEKVIIFGMGKRKCIGETIARWEVFLFLAILLQRVEF
SVPLGVKVDMTPIYGLTMKHACCEHFQMQLRS
Drug Target 1 [top]
Target 1 ID 631
Target 1 Name 3-hydroxy-3-methylglutaryl-coenzyme A reductase
Target 1 Synonyms
  1. EC 1.1.1.34
  2. HMG-CoA reductase
Target 1 Gene Name HMGCR
Target 1 Protein Sequence >3-hydroxy-3-methylglutaryl-coenzyme A reductase 
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSS
DIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTG
LNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIG
VGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFAR
VLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKR
IEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVT
QKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNS
SLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYK
LETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGV
AGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRAC
DSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMI
SKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREV
LKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITL
MEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLAR
IVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA
Target 1 Number of Residues 902
Target 1 Molecular Weight 97477
Target 1 Theoretical pI 6.72
Target 1 GO Classification
Function
hydroxymethylglutaryl-CoA reductase (NADPH) activity
hydroxymethylglutaryl-CoA reductase (NADPH) activity
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on CH-OH group of donors
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
hydroxymethylglutaryl-CoA reductase (NADPH) activity
Process
primary metabolism
lipid metabolism
physiological process
metabolism
biosynthesis
Component
organelle membrane
endoplasmic reticulum membrane
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Lipid transport and metabolism
Target 1 Specific Function This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis
Target 1 Pathways
Name SMPDB Link KEGG Link
Biosynthesis of steroids map00100 Link Image
Target 1 Reactions
  • (R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 10-39
  • 57-78
  • 90-114
  • 124-149
  • 160-187
  • 192-220
  • 315-339
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 306865 Link Image
Target 1 UniProtKB/Swiss-Prot ID P04035 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name HMDH_HUMAN Link Image
Target 1 PDB ID 1HWL Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Endoplasmic reticulum
  • endoplasmic reticulum membrane
  • multi-pass membrane protein. Peroxisome
  • pero
Target 1 Gene Sequence >2667 bp 
ATGTTGTCAAGACTTTTTCGAATGCATGGCCTCTTTGTGGCCTCCCATCCCTGGGAAGTC
ATAGTGGGGACAGTGACACTGACCATCTGCATGATGTCCATGAACATGTTTACTGGTAAC
AATAAGATCTGTGGTTGGAATTATGAATGTCCAAAGTTTGAAGAGGATGTTTTGAGCAGT
GACATTATAATTCTGACAATAACACGATGCATAGCCATCCTGTATATTTACTTCCAGTTC
CAGAATTTACGTCAACTTGGATCAAAATATATTTTGGGTATTGCTGGCCTTTTCACAATT
TTCTCAAGTTTTGTATTCAGTACAGTTGTCATTCACTTCTTAGACAAAGAATTGACAGGC
TTGAATGAAGCTTTGCCCTTTTTCCTACTTTTGATTGACCTTTCCAGAGCAAGCACATTA
GCAAAGTTTGCCCTCAGTTCCAACTCACAGGATGAAGTAAGGGAAAATATTGCTCGTGGA
ATGGCAATTTTAGGTCCTACGTTTACCCTCGATGCTCTTGTTGAATGTCTTGTGATTGGA
GTTGGTACCATGTCAGGGGTACGTCAGCTTGAAATTATGTGCTGCTTTGGCTGCATGTCA
GTTCTTGCCAACTACTTCGTGTTCATGACTTTCTTCCCAGCTTGTGTGTCCTTGGTATTA
GAGCTTTCTCGGGAAAGCCGCGAGGGTCGTCCAATTTGGCAGCTCAGCCATTTTGCCCGA
GTTTTAGAAGAAGAAGAAAATAAGCCGAATCCTGTAACTCAGAGGGTCAAGATGATTATG
TCTCTAGGCTTGGTTCTTGTTCATGCTCACAGTCGCTGGATAGCTGATCCTTCTCCTCAA
AACAGTACAGCAGATACTTCTAAGGTTTCATTAGGACTGGATGAAAATGTGTCCAAGAGA
ATTGAACCAAGTGTTTCCCTCTGGCAGTTTTATCTCTCTAAAATGATCAGCATGGATATT
GAACAAGTTATTACCCTAAGTTTAGCTCTCCTTCTGGCTGTCAAGTACATCTTCTTTGAA
CAAACAGAGACAGAATCTACACTCTCATTAAAAAACCCTATCACATCTCCTGTAGTGACA
CAAAAGAAAGTCCCAGACAATTGTTGTAGACGTGAACCTATGCTGGTCAGAAATAACCAG
AAATGTGATTCAGTAGAGGAAGAGACAGGGATAAACCGAGAAAGAAAAGTTGAGGTTATA
AAACCCTTAGTGGCTGAAACAGATACCCCAAACAGAGCTACATTTGTGGTTGGTAACTCC
TCCTTACTCGATACTTCATCAGTACTGGTGACACAGGAACCTGAAATTGAACTTCCCAGG
GAACCTCGGCCTAATGAAGAATGTCTACAGATACTTGGGAATGCAGAGAAAGGTGCAAAA
TTCCTTAGTGATGCTGAGATCATCCAGTTAGTCAATGCTAAGCATATCCCAGCCTACAAG
TTGGAAACTCTGATGGAAACTCATGAGCGTGGTGTATCTATTCGCCGACAGTTACTTTCC
AAGAAGCTTTCAGAACCTTCTTCTCTCCAGTACCTACCTTACAGGGATTATAATTACTCC
TTGGTGATGGGAGCTTGTTGTGAGAATGTTATTGGATATATGCCCATCCCTGTTGGAGTG
GCAGGACCCCTTTGCTTAGATGAAAAAGAATTTCAGGTTCCAATGGCAACAACAGAAGGT
TGTCTTGTGGCCAGCACCAATAGAGGCTGCAGAGCAATAGGTCTTGGTGGAGGTGCCAGC
AGCCGAGTCCTTGCAGATGGGATGACTCGTGGCCCAGTTGTGCGTCTTCCACGTGCTTGT
GACTCTGCAGAAGTGAAAGCCTGGCTCGAAACATCTGAAGGGTTCGCAGTGATAAAGGAG
GCATTTGACAGCACTAGCAGATTTGCACGTCTACAGAAACTTCATACAAGTATAGCTGGA
CGCAACCTTTATATCCGTTTCCAGTCCAGGTCAGGGGATGCCATGGGGATGAACATGATT
TCAAAGGGTACAGAGAAAGCACTTTCAAAACTTCACGAGTATTTCCCTGAAATGCAGATT
CTAGCCGTTAGTGGTAACTATTGTACTGACAAGAAACCTGCTGCTATAAATTGGATAGAG
GGAAGAGGAAAATCTGTTGTTTGTGAAGCTGTCATTCCAGCCAAGGTTGTCAGAGAAGTA
TTAAAGACTACCACAGAGGCTATGATTGAGGTCAACATTAACAAGAATTTAGTGGGCTCT
GCCATGGCTGGGAGCATAGGAGGCTACAACGCCCATGCAGCAAACATTGTCACCGCCATC
TACATTGCCTGTGGACAGGATGCAGCACAGAATGTTGGTAGTTCAAACTGTATTACTTTA
ATGGAAGCAAGTGGTCCCACAAATGAAGATTTATATATCAGCTGCACCATGCCATCTATA
GAGATAGGAACGGTGGGTGGTGGGACCAACCTACTACCTCAGCAAGCCTGTTTGCAGATG
CTAGGTGTTCAAGGAGCATGCAAAGATAATCCTGGGGAAAATGCCCGGCAGCTTGCCCGA
ATTGTGTGTGGGACCGTAATGGCTGGGGAATTGTCACTTATGGCAGCATTGGCAGCAGGA
CATCTTGTCAAAAGTCACATGATTCACAACAGGTCGAAGATCAATTTACAAGACCTCCAA
GGAGCTTGCACCAAGAAGACAGCCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID HMGCR Link Image
Target 1 GenAtlas ID HMGCR Link Image
Target 1 HGNC ID HGNC:5006 Link Image
Target 1 Chromosome Location 5
Target 1 Locus 5q13.3-q14
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Istvan ES, Palnitkar M, Buchanan SK, Deisenhofer J: Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. EMBO J. 2000 Mar 1;19(5):819-30. [PubMed Link Image]
  3. Luskey KL, Stevens B: Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation. J Biol Chem. 1985 Aug 25;260(18):10271-7. [PubMed Link Image]
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]

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